Single nucleotide polymorphisms in 5-HT receptors in the etiology of premature ejaculation.

INTRODUCTION AND OBJECTIVES: Premature ejaculation (PE) is characterized by shorter intravaginal ejaculation latency time than it is acceptable for the patient or partner. It is thought that lifelong PE is a neurobiological dysfunction associated with genetic predisposition and with central serotonin neurotransmission dysfunction in receptors. To contribute to the understanding the genetic etiology of lifelong PE, it was planned to compare the 5-HT2C receptor gene rs3813929, rs518147, 5-HT1A receptor gene rs6295, 5-HT1B receptor gene rs11568817 of lifelong PE patients to healthy controls. MATERIALS AND METHODS: For this purpose, 100 patients with premature ejaculation and 100 healthy controls were included in the study. Blood samples for DNA extraction were obtained. Appropriate procedures were applied to the probes (rs3813929, rs518147, rs6295, rs11568817) suitable for the DNA studied. RESULTS: A statistically significant relationship was found between the rs11568817 polymorphism (p=0.019) in the 5-HT1B receptor gene and the rs518147 polymorphism (p=0.016) in the 5-HT2C receptor gene. Also, no statistically significant relationship was found between 5-HT1A receptor gene rs6295 polymorphism and 5-HT2C receptor gene rs3813929 polymorphism and lifelong PE. CONCLUSIONS: The relationship between rs3813929 and rs11568817 polymorphisms with lifelong PE was confirmed. Repeating the study in larger sample groups could be useful in determining the genetic etiology of PE.

In vitro study on immune response modifiers as novel medical treatment options for cholesteatoma.

OBJECTIVES: To investigate cytokine profile of cholesteatoma and to collect information about important intercellular signaling pathways by establishing two different cell culture models, to block important intercellular signaling pathways in cholesteatoma by applying immune system modifier drugs to develop alternative medical therapy options for cholesteatoma. METHODS: To observe the pathogenesis of cholesteatoma and to apply the immunomodulatory drugs, cholesteatoma tissue culture models were constituted with HEKa cells and cholesteatoma keratinocytes, which were obtained from 3 patients who underwent operations for cholesteatoma. Medicines including 5-fluorourasil, imiquimod, cyclosporine, and tacrolimus were applied on both cholesteatoma keratinocytes and HEKa cells. After 48 h of incubation, IL-1, IL-6, IL-8, IL-10, TNF-α, and Ki67 levels were measured to determine cell viability rates. RESULTS: In the cholesteatoma control group, IL-6 and TNF-α levels were found higher than in the HEKa control group. All repurposed drugs in the study demonstrated anti-inflammatory, anti-proliferative, and cytotoxic effects on cholesteatoma. Imiquimod and tacrolimus in particular are potential treatment prospects for cholesteatoma due to their strong anti-inflammatory and cytotoxic effects. CONCLUSION: Medical therapy options for cholesteatoma are still missing and surgery is not the ultimate solution. We have focused on intercellular inflammatory processes, which play significant roles in the pathogenesis of cholesteatoma in our paper. Inflammation and proliferation of cholesteatoma decreased after all repurposed drug applications in our study. Anti-inflammatory and anti-proliferative effects of tacrolimus and imiquimod was more significant than other drugs in the study. For this reason, tacrolimus and imiquimod should be examined in depth with in vivo studies in terms of efficacy and safety for medical treatment of cholesteatoma.

Association of Nicotine Use Disorder with Neurexin 3 Gene Polymorphisms. / Nikotin Kullanim Bozuklugunun Neurexin 3 Gen Polimorfizmi ile Iliskisi.

OBJECTIVE: In this study, we aimed to investigate the Neurexin 3 gene (NRXN3) polymorphisms in the rs 221473, rs 221497, rs1004212 and rs11624704 regions in relation to nicotine use disorder (NUD) in the Turkish population. METHOD: Power analysis indicated that the NUD group and the control group of this study should each comprise 200 participants in the 18-65 year age range. The NUD group consisted of individuals without a psychiatric first axis disorder except for NUD, mental retardation, past head trauma or a neurological disorder, who had smoked minimally10 cigarettes per day for at least 1 year. The control group included individuals without a serious chronic physical illness, a previous psychiatric disorder or mental retardation and who responded "no" to the question "have you ever smoked?" A sociodemographic questionnaire and the Fageström nicotine dependence scale (FNDS) for the NUD group were utilized. Venous blood samples of all participants were taken into tubes containing EDTA (ethylene daimine tetra acetic acid) for DNA extraction. Duplex fluorescence melting curve analysis was used for genotype detection and differentiation. RESULTS: The individuals carrying the AC allele and the AG allele at the rs11624704 and the rs1004212 regions respectively had a high risk of being addicted to cigarettes. CONCLUSION: This is first study investigating the relationship of the NRXN3 gene and nicotine addiction in the Turkish population. It was observed that the risk of NUD in the Turkish population may be related to the Neurexin gene.

Association of Nicotine Use Disorder with Neurexin 3 Gene Polymorphisms. / Nikotin Kullanim Bozuklugunun Neurexin 3 Gen Polimorfizmi ile Iliskisi.

OBJECTIVE: In this study, we aimed to investigate the Neurexin 3 gene (NRXN3) polymorphisms in the rs 221473, rs 221497, rs1004212 and rs11624704 regions in relation to nicotine use disorder (NUD) in the Turkish population. METHOD: Power analysis indicated that the NUD group and the control group of this study should each comprise 200 participants in the 18-65 year age range. The NUD group consisted of individuals without a psychiatric first axis disorder except for NUD, mental retardation, past head trauma or a neurological disorder, who had smoked minimally10 cigarettes per day for at least 1 year. The control group included individuals without a serious chronic physical illness, a previous psychiatric disorder or mental retardation and who responded "no" to the question "have you ever smoked?" A sociodemographic questionnaire and the Fageström nicotine dependence scale (FNDS) for the NUD group were utilized. Venous blood samples of all participants were taken into tubes containing EDTA (ethylene daimine tetra acetic acid) for DNA extraction. Duplex fluorescence melting curve analysis was used for genotype detection and differentiation. RESULTS: The individuals carrying the AC allele and the AG allele at the rs11624704 and the rs1004212 regions respectively had a high risk of being addicted to cigarettes. CONCLUSION: This is first study investigating the relationship of the NRXN3 gene and nicotine addiction in the Turkish population. It was observed that the risk of NUD in the Turkish population may be related to the Neurexin gene.

Effects of S1P1 and S1P3 in ER+ and ER- Breast Cancer Cells.

BACKGROUND/AIM: In this study, sphingosine-1-phosphate receptor-1 (S1P1) and S1P3 receptors were silenced to evaluate proliferation, adhesion, viability and lateral motility in estrogen receptor-negative MCF-7 and estrogen receptor-positive MDA-MB-231 breast cancer cells. MATERIALS AND METHODS: Groups of MCF-7 and MDA-MB-231 cells with: no small interfering RNA (siRNA); siRNA with no target; S1P1-silencing siRNA; S1P3-silencing siRNA; and siRNAs silencing both S1P1, and S1P3 were examined for this purpose at 24, 48 and 72 h after intervention. RESULTS: Viability of cells was reduced due to suppression of S1P1/S1P3. While no change was observed in the proliferation of MCF-7 cells, the proliferation of S1P1/S1P3-suppressed MDA-MB-231 cells was reduced. S1P1/S1P3 suppression resulted in reduction of adhesion of MCF-7 cells, but to an increase of MDA-MB-231 cells. Lateral motility was reduced in all S1P1/S1P3-suppressed groups. CONCLUSION: Silencing the receptors simultaneously rather than separately was more effective. Additionally, the different characteristics of cancer cells affected the proliferation and adhesion of cells differently. This difference may be associated with the estrogen receptors in the cells.